种系基因检测中的变异分类对于患者及其家人得到适当的护理是必要的。使用美国医学遗传学学院和分子病理学协会推荐的标准和指南，将变异分为致病性 (P)、可能致病性 (LP)、不确定意义 (VUS)、可能良性 (LB) 和良性 (B) ，对特定基因进行修饰。随着文献不断迅速扩大，证据不断积累，先前的分类可以相应更新。在这项研究中，我们的目标是描述安大略省的变异重新分类特征。提交了 2012 年 1 月至 2022 年 4 月在安大略省遗传性癌症诊所就诊的患者的 DNA 样本进行测试。患者符合省遗传性癌症综合征或多囊肾病检测资格标准。重新分类事件被确定为在其更广泛的重要性类别内（B 到 LB 或反之亦然，或 P 到 LP 或反之亦然）或在其更广泛的重要性类别之外（即，从 B/LB 或 VUS 或 P/ LP，从 P/LP 到 VUS 或 B/LB，或从 VUS 到任何其他类别）。在本研究中包含的 8075 个独特变体中，重新评估了 23.7% (1912) 个变体，并对 7.2% (578) 个变体进行了重新评估被重新分类。其中，351 个 (60.7%) 变异被重新分类，超出了其更广泛的意义类别。总体而言，336 个 (58.1%) 变体的最终分类存在显着差异。重要的是，大多数重新分类的变异被降级为更良性的分类（n=245；72.9%）。值得注意的是，大多数重新分类的 VUS 被降级为 B/LB（n=233；84.7%）。重新评估时变异体重新分类的可能性很高。大多数重新分类的变体被降级为更良性的分类。我们的研究结果强调了定期变异重新评估的重要性，以确保为患者及其家人提供及时和适当的护理。©作者（或其雇主）2024。禁止商业重复使用。请参阅权利和权限。英国医学杂志出版。

Variant classification in the setting of germline genetic testing is necessary for patients and their families to receive proper care. Variants are classified as pathogenic (P), likely pathogenic (LP), uncertain significance (VUS), likely benign (LB) and benign (B) using the standards and guidelines recommended by the American College of Medical Genetics and the Association for Molecular Pathology, with modifications for specific genes. As the literature continues to rapidly expand, and evidence continues to accumulate, prior classifications can be updated accordingly. In this study, we aim to characterise variant reclassifications in Ontario.DNA samples from patients seen at hereditary cancer clinics in Ontario from January 2012 to April 2022 were submitted for testing. Patients met provincial eligibility criteria for testing for hereditary cancer syndromes or polycystic kidney disease. Reclassification events were determined to be within their broader category of significance (B to LB or vice versa, or P to LP or vice versa) or outside of their broader category as significance (ie, significant reclassifications from B/LB or VUS or P/LP, from P/LP to VUS or B/LB, or from VUS to any other category).Of the 8075 unique variants included in this study, 23.7% (1912) of variants were reassessed, and 7.2% (578) of variants were reclassified. Of these, 351 (60.7%) variants were reclassified outside of their broader category of significance. Overall, the final classification was significantly different for 336 (58.1%) variants. Importantly, most reclassified variants were downgraded to a more benign classification (n=245; 72.9%). Of note, most reclassified VUS was downgraded to B/LB (n=233; 84.7%).The likelihood for reclassification of variants on reassessment is high. Most reclassified variants were downgraded to a more benign classification. Our findings highlight the importance of periodic variant reassessment to ensure timely and appropriate care for patients and their families.© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.